Psilocybin for Healthy Subjects

Overseen By

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Johns Hopkins University

Must not be taking: Psychoactive medications, MAOIs

Disqualifiers: Pregnancy, Cardiovascular conditions, Epilepsy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how psilocybin, a compound from certain mushrooms, affects thoughts and brain activity. Researchers will use tools like brain scans and computer tests to observe these changes. The trial involves two groups: one receiving psilocybin first and a placebo (a dummy treatment) later, and the other starting with the placebo. Suitable participants are healthy, English-speaking individuals who have tried psychedelic drugs at least five times. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore its effects.

Will I have to stop taking my current medications?

If you are currently taking psychoactive prescription medications or medications with a primary serotonergic effect regularly, you will need to stop taking them before participating. For 'as needed' medications, there is a required waiting period before the psilocybin sessions.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that psilocybin is usually safe for humans. In one study, researchers tested a form of psilocybin called COMP360 at various doses, including 10mg, similar to the dose used in this trial. Most side effects were mild to moderate, such as headaches, nausea, and temporary anxiety, while serious side effects were rare.

Another study with healthy volunteers found that psilocybin's effects were predictable and manageable. The trials aimed to identify common and serious side effects, and most issues reported were mild and resolved on their own.

Psilocybin is being tested for safety in different situations, and evidence so far suggests it is generally safe when used in a controlled clinical setting. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for healthy subjects?

Psilocybin is unique because it offers a new approach for affecting mental health by acting on serotonin receptors in the brain, which is different from traditional antidepressants that often target serotonin reuptake. Researchers are excited about psilocybin because its active ingredient, derived from certain mushrooms, could lead to rapid and potentially long-lasting effects after just one dose. Unlike many current treatments that require daily administration and weeks to take effect, psilocybin's impact can be felt within hours and might offer sustained benefits after a single session.

What evidence suggests that psilocybin might be an effective treatment for changing thoughts and brain activity?

This trial will compare the effects of psilocybin with a placebo in healthy subjects. Research has shown that psilocybin, a substance found in some mushrooms, may alter thought and emotion. Studies have found that psilocybin can enhance emotional processing, particularly in individuals with treatment-resistant depression. This suggests it might increase emotional awareness and understanding. Other research indicates that psilocybin can improve mood and mental health. Although more studies are necessary, early results are promising for its potential to positively impact brain function and mental well-being. ^{2 4 6 7 8}

Who Is on the Research Team?

Frederick S Barrett, PhD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Participants must be healthy adults aged 18-75, vaccinated against COVID-19, fluent in English with at least high school education. They should have prior experience with psychedelics and agree to avoid psychoactive substances and certain medications before sessions. Pregnant or nursing women, individuals with cardiovascular issues, epilepsy, diabetes on insulin, psychiatric disorders or those taking serotonergic medications are excluded.

Inclusion Criteria

Have given written informed consent

Agree to refrain from using psychoactive drugs, alcoholic beverages, and nicotine within 24 hours of each drug administration

Agree not to take any 'as-needed' medications on the mornings of drug sessions

Exclusion Criteria

Left-handedness

Current or past history within the last five years of meeting DSM-5 criteria for moderate or severe alcohol or drug use disorder

I have diabetes that requires insulin or have had low blood sugar with diabetes pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either psilocybin or placebo in a double-blind, placebo-controlled, within-subject, full cross-over study

8 weeks

Multiple visits for drug administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Psilocybin

Trial Overview The study examines the effects of psilocybin versus a placebo on thought processes and brain activity using EEG and MRI scans. Participants will perform computerized tasks while their brain responses are monitored to understand how this psychedelic compound affects them.

How Is the Trial Designed?

Group I: Psilocybin First Experimental Treatment 2 Interventions

Psilocybin (10mg) will be administered one time orally as a capsule taken with water. Expected duration of acute effects is approximately 6 hours. After a period of a washout, participants will switch to the placebo intervention.

Group II: Placebo First Placebo Group 2 Interventions

Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water. After a period of a washout, participants will switch to the Psilocybin intervention.

Psilocybin is already approved in United States, European Union for the following indications:

Approved in United States as Psilocybin for:

• Treatment-resistant depression (TRD) under Breakthrough Therapy designation

Approved in European Union as Psilocybin for:

• Treatment-resistant depression (TRD) under PRIME designation

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

A meta-analysis of psilocybin studies found that higher doses of psilocybin are associated with stronger subjective experiences, particularly in areas like perceptual alterations and ego dissolution, based on data from standardized questionnaires.

Challenging experiences were less affected by dose, suggesting that individual and environmental factors also play a significant role in the psilocybin experience, indicating that these findings are most relevant in controlled settings rather than recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response relationships of psilocybin-induced subjective experiences in humans. Hirschfeld, T., Schmidt, TT.[2022]

Psilocybin-containing mushrooms, commonly known as hallucinogenic or 'magic' mushrooms, rapidly affect the central nervous system within 0.5-1 hour of ingestion, leading to effects such as ataxia, hyperkinesis, and hallucinations.

The review discusses the significant toxicity associated with these mushrooms, highlighting the need for awareness and understanding of their pharmacology, clinical effects, and potential treatment for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hallucinogenic mushrooms]. Reingardiene, D., Vilcinskaite, J., Lazauskas, R.[2018]

This study found that the binding of serotonin 2A receptors (5-HT2AR) in the brain can predict how long the peak effects of psilocybin last and how quickly individuals return to normal consciousness after its effects wear off.

Higher levels of 5-HT2AR binding were associated with lower scores on the Mystical Experience Questionnaire, suggesting that individual differences in receptor availability may influence the subjective experience of psilocybin, which could have implications for its therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain serotonin 2A receptor binding predicts subjective temporal and mystical effects of psilocybin in healthy humans. Stenbæk, DS., Madsen, MK., Ozenne, B., et al.[2022]

Psilocybin, a hallucinogenic compound found in certain mushrooms, has been associated with increasing rates of drug abuse, highlighting the need for comprehensive pharmacological understanding.

Despite its historical use in the 1960s for experimental medical purposes, recent research has only begun to uncover the pharmacological properties of psilocybin, indicating a gap in knowledge that needs to be addressed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacology of psilocybin. Passie, T., Seifert, J., Schneider, U., et al.[2016]

A 30-year-old man experienced severe symptoms, including vomiting and muscle pain, after receiving an intravenous injection of Psilocybe mushroom extract, highlighting the potential dangers of using hallucinogenic substances in non-traditional ways.

The patient showed rapid improvement with supportive care, suggesting that while the effects of Psilocybe mushrooms can be serious, timely medical intervention can effectively manage the symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous mushroom poisoning. Curry, SC., Rose, MC.[2019]

A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quickly and accurately measure the levels of psilocybin and psilocin in magic truffles, with high precision and reliability (r² > 0.99).

The study found that only psilocybin was present in the examined Psilocybe sclerotia, with concentrations ranging from 59.3 to 167.8 µg per 100 mg of fresh truffles, indicating variability in psilocybin content.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magic truffles or Philosopher's stones: a legal way to sell psilocybin? Pellegrini, M., Rotolo, MC., Marchei, E., et al.[2019]

In a case study involving 'magic mushroom' intake, psilocin was detected in urine, primarily in its glucuronide form, indicating that enzymatic hydrolysis is essential for accurate analysis.

The study established a reliable GC-MS method for detecting psilocin, revealing that most of the psilocin in serum was also conjugated, with very low concentrations of free psilocin found in both urine and serum.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of psilocin in body fluids. Sticht, G., Käferstein, H.[2019]

Psilocybin shows promising effects in alleviating anxiety, depression, and emotional distress in palliative care patients, with a favorable safety profile, based on recent studies and reports.

Despite its potential benefits, psilocybin is not yet approved for therapeutic use in the U.S., and significant barriers exist for access, particularly for vulnerable populations like the elderly and those in palliative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psilocybin in Palliative Care: An Update. Whinkin, E., Opalka, M., Watters, C., et al.[2023]

There is a growing trend among young people to consume wild Psilocybin mushrooms for their hallucinogenic effects, but this practice carries risks.

The report highlights seven cases of mushroom overdosage, stressing that while Psilocybin mushrooms are generally considered harmless, there is a significant danger of accidentally consuming toxic mushroom species that can cause serious harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The danger of hallucinogenic mushrooms. Mills, PR., Lesinskas, D., Watkinson, G.[2017]

The study identified high levels of the psychoactive compounds psilocin and psilocybin in three species of mushrooms: Psilocybe semilanceata, Psilocybe bohemica, and Psilocybe arcana, indicating their potential for psychoactive effects.

Using gas chromatography-mass spectrometry (GC/MS) for quantification, the research provides a detailed analysis of the psilocin and psilocybin content in various mushroom species, contributing to the understanding of their psychoactive properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Levels of psilocybin and psilocin in various types of mushrooms]. Stríbrný, J., Borovicka, J., Sokol, M.[2016]

In a study examining the effects of Psilocybe cubensis and Panaeolus cyanescens mushrooms on heart cells, the extracts did not worsen hypertrophy caused by endothelin-1 and provided protection against TNF-α-induced cell injury.

The findings suggest that these mushroom extracts can be safely used in controlled conditions for potential therapeutic benefits in heart disease, although caution is advised with higher concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushroom extracts on endothelin-1-induced hypertrophy and cell injury in cardiomyocytes. Nkadimeng, SM., Steinmann, CML., Eloff, JN.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0165032724020494

The role of the psychedelic experience in psilocybin ... To determine the relationships between psilocybin dose, psychedelic experiences, and therapeutic outcome in treatment-resistant depression.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05624268

Efficacy, Safety, and Tolerability of COMP360 in ... This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study.

3. compasspathways.com compasspathways.com/our-work/comp360-psilocybin-treatment-in-trd/

COMP360 psilocybin treatment in TRD This trial assessed the safety and efficacy of COMP360 psilocybin treatment in three doses: 1mg, 10mg, 25mg. The results, published in the New England Journal ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12226623/

Psilocybin therapy for treatment resistant depression Therapeutic administration of psychedelics has shown significant potential in historical accounts and recent clinical trials in the treatment of depression ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11612538/

Impact of psilocybin on cognitive function: A systematic ... Emotional processing was positively modified, particularly in TRD patients. Psilocybin was observed to enhance emotional empathy without ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03775200

NCT03775200 | The Safety and Efficacy of Psilocybin in ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05312151

NCT05312151 | The Safety and Tolerability of COMP360 in ... They are usually conducted with healthy volunteers, and the goal is to determine the drug's most frequent and serious adverse events and, often, how the drug is ...

8. isrctn.com isrctn.com/ISRCTN17905443

A study carried out on healthy volunteers to understand ... COMP360 is being investigated as a drug for depression. This study aims to investigate how safe and well tolerated is the administration of four different doses ...